The Lemon Flavonoid Eriomin® Suppresses Pituitary-Adrenal Axis Activity in Aged Rats

Abstract

The lemon flavonoid extract Eriomin^® (LE), which is rich in eriocitrin, has demonstrated antioxidant and anti-inflammatory properties in both animal and human studies. Given the established interplay among aging, oxidative stress, and inflammation, this study investigated the influences of LE on the pituitary-adrenal (PA) axis in aged rats and its potential to mitigate age-related physiological changes in this system. The effects of LE (40 mg/kg/day suspended in sunflower oil) on the morphofunctional properties of the PA axis were studied in 24-month-old male Wistar rats following four weeks of oral treatment. Control groups included vehicle-treated (sunflower oil; CON) and untreated intact controls (ICON). Stereological and imaging analyses revealed no significant changes in pituitary ACTH cells; however, Pomc gene expression was significantly downregulated in the LE group compared to both controls (p ≤ 0.05). LE treatment resulted in a significant reduction in adrenal gland weight (p ≤ 0.05), adrenal gland volume (p ≤ 0.01), zona fasciculata (ZF) volume (p ≤ 0.01) and ZF cell volume (p ≤ 0.05). These changes were accompanied by a significant decrease in serum corticosterone levels (p ≤ 0.05). In conclusion, LE downregulated PA axis activity in aged rats. Considering the association between age-related increases in PA activity and adverse health outcomes, citrus flavonoid extracts such as LE may hold promise as anti-aging supplements aimed at mitigating age-related stress dysregulation.

Keywords: adrenal gland; aged rat; healthy ageing; lemon flavonoid extract Eriomin®; pituitary gland.

Figure 1

Chemical structures of the main citrus flavonoids in Eriomin^®.

Figure 2

ACTH immunopositivity in the pituitary gland of aged rats in the intact control group (ICON, A), the sunflower-oil control group (CON, B), and the group treated with the lemon flavonoid extract Eriomin^® (LE, C). ACTH cells (arrows), blood vessels (asterisks); scale bar = 20 μm.

Figure 3

Volume (A) and optical density (B) of ACTH cells and Pomc mRNA expression (C) in aged rats in the intact control group (ICON), the sunflower-oil control group (CON) and the lemon flavonoid extract Eriomin^® group (LE). Data are presented as mean ± SEM (n = 6/group); one-way ANOVA test followed by Dunnett’s post hoc test (with CON serving as the control group); * p ≤ 0.05.

Figure 4

Sirius red- (A–C), Novelli- (D–F) and VEGF immune- (G–I) stained sections of the adrenal gland from aged rats in the intact control group (ICON), the sunflower-oil control group (CON), and the lemon flavonoid extract Eriomin^® group (LE); zona glomerulosa (ZG), zona fasciculata (ZF), zona reticularis (ZR); blood vessels (arrows); scale = 50 µm (A–C,G–I); scale = 20 µm (D–F and inserted micrographs).

Figure 5

Hematoxylin–eosin-stained sections (A–C), the absolute volume of the adrenal gland and its zona fasciculata (D), the absolute volume of individual cells within the zona fasciculata (E), and serum corticosterone concentration (F) in the adrenal gland from aged rats in the intact control group (ICON), the sunflower-oil control group (CON) and the lemon flavonoid extract Eriomin^® group (LE); scale = 50 µm (A–C), scale = 20 µm inserted micrographs. Data are presented as means ± SEM (n = six/group); one-way ANOVA test followed by Dunnett’s post hoc test (with CON serving as the control group); * p ≤ 0.05, ** p ≤ 0.01.